Unique Associations between Insulin-Like Growth Factor Binding Protein-1, Insulin-Like Growth Factor-1 and T Cell Immunoglobulin Mucin 3 in Successful Twin Pregnancies Conceived with Donor Oocytes.

Giovanni Sisti,Mariarosaria Di Tommaso,Astrid Parenti,Roberta Cuzzola,Sara Paccosi,Steven S Witkin,Viola Seravalli

doi:10.3390/medicina55050144

Abstract

Background and Objectives: To investigate if pregnancies conceived using an oocyte donor necessitate an alteration in immune regulation, we compared concentrations of insulin-like growth factor binding protein (IGFBP)-1, insulin-like growth factor (IGF)-1 and T cell immunoglobulin mucin-3 (Tim-3) in women with ongoing successful twin pregnancies conceived spontaneously, using assisted reproductive technologies that utilized homologous oocytes or with donor oocytes. Differences in levels of these immune modulatory proteins may be magnified and easier to detect in twin as compared to singleton pregnancies. Methods: In this prospective study IGFBP-1 and IGF-1 were measured in sera and Tim-3 in lysates of peripheral blood mononuclear cells (PBMCs) by ELISA. Results: Median IGFBP-1 levels were lower in women with donor oocytes (41.4 ng/ml) as compared to those with a spontaneous conception (51.2 ng/mL) or who conceived with various assisted reproduction protocols using homologous oocytes (52.4 ng/mL) (p < 0.001). IGF-1 and Tim-3 levels were comparable in each group. The IGFBP-1 level was inversely correlated to the IGF-1 concentration only in women with donor oocytes (p = 0.032). IGFBP-1 and Tim-3 levels were similarly negatively correlated in the donor oocyte group (p = 0. 012). Women in the assisted reproduction group who conceived following intracytoplasmic sperm injection were the only other group in which IGFBP-1 and Tim-3 were negatively correlated (p = 0.018). Conclusions: Down-regulation of IGFBP-1 production in pregnancies conceived with donor oocytes may reduce the extent of pro-inflammatory immunity and contribute to successful outcome in totally allogeneic pregnancies.

Highlights

Pregnancies involving an oocyte donor differ from conventional gestations
Group 1 was composed of women with spontaneous conceptions; group 2 was women who conceived by assisted reproduction, either merely ovarian stimulation with clomiphene citrate (3), intrauterine insemination (3), in vitro fertilization and embryo transfer (IVF-ET) (20), intracytoplasmic sperm injection (ICSI) (18); group 3 was 25 women who were pregnant by IVF using oocyte donation
The median level of insulin-like growth factor binding protein (IGFBP)-1 was significantly lower in women who were pregnant with donor oocytes (p = 0.001)

Summary

Introduction

Pregnancies involving an oocyte donor differ from conventional gestations. In the absence of a corpus luteum, the post-conception rise in estrogen and progesterone do not occur and these essential hormones have to be exogenously supplied [1]. The maternal immune system must respond to a fetus that expresses antigens derived from foreign paternal chromosomes (semi-allogeneic). When fetuses are derived from fertilization of oocytes from a third-party oocyte donor and implanted in a second woman, both paternal and maternal antigens expressed by the embryo are foreign. This places an additional burden on the maternal immune system to effectively regulate the extent of reactivity to antigens from two exogenous sources. Results: Median IGFBP-1 levels were lower in women with donor oocytes (41.4 ng/ml) as compared to those with a spontaneous conception (51.2 ng/mL) or who conceived with various assisted reproduction protocols using homologous oocytes (52.4 ng/mL) (p < 0.001). Women in the assisted reproduction group who conceived following intracytoplasmic sperm injection were the only other group in which

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Conclusion